Dr. Georgina Long

Melanoma is a key cancer type for developing and testing immunotherapies prior to broader clinical application across other malignancies.

Understanding How to Advance Immunotherapy Strategy Models in Melanoma

Melanoma is a key cancer type for developing and testing immunotherapies prior to broader clinical application across other malignancies, Dr. Georgina Long explained in an interview with CURE.

“Melanoma is a great cancer to test immunotherapies in because we're very well benchmarked; we don't have any legacy drugs, meaning we don't have a history of activity of drug therapies that dates back to the 1960s with chemotherapy,” said Long. “Nothing worked. So, when I came into the field, patients were dying, literally within six to nine months. When you have that lack of activity, you have a lot of ability to think outside the box and push the field forward.”

Long is a professor and medical director at the Melanoma Institute Australia, as well as the chair of Melanoma Medical Oncology and Translational Research at MIA and Royal North Shore Hospital, The University of Sydney.

 about her perspective on the history of immunotherapy treatment advancements starting in melanoma.

So, melanoma is a great cancer to test immunotherapies in because we're very well benchmarked, and we don't have legacy drugs, meaning we don't have a history of active drug therapies in melanoma that dates back to the 1960s with chemotherapy. Nothing worked. So, when I entered the field, patients were dying, literally within six to nine months. And when you have that lack of activity, you have a lot of ability to think outside the box and push the field forward.

In melanoma, we've always known it had a relationship with the immune system. We've seen spontaneous remissions in melanoma. There was always this weird history of spontaneous remissions in patients who had melanoma throughout their lungs, and it just disappeared on its own. We also see a lot of T cells in some primary melanomas, so the original melanoma on the skin. So we've always known that, and we can see regression on primary melanomas as well, where they start to show evidence of shrinkage on their own.

So, we've tried to leverage that over many decades with TIL therapy, so tumor-infiltrating lymphocyte therapy, but we were never able to get that high level of cure until we started working with checkpoint inhibitors back in about 2005 actually. And that first one was anti-CTLA4, where we saw some evidence of activity in the phase 1 trials. And then building on that, we then worked on anti-PD1, and that's where we saw this incredible shift. All of a sudden, going from no one surviving the disease—this is advanced melanoma we're talking about, where it spreads around the body, like to the brain, the bones, the lungs—all of a sudden, we were going from seeing practically no one survive, it was almost universally fatal, it was the cancer you did not want to get in advanced form because nothing worked, to seeing 50% of people, especially when we use combination checkpoints, cured.

But there's still about 45% of people who are dying quite quickly. Probably 25% die really quickly. Every month, I have someone who dies within weeks of their diagnosis of stage 4 melanoma, and this is what inspires me and keeps me working hard. Because for the cured people, we've done survivorship studies at two years, they don't want to know, or they're actually leading really good lives with high quality of life. They don't have a lot of survivorship needs. They just want to get on with their life, and that's because it's a treatment, and then you're cured, and that's it. It's not an ongoing process over years where you try this and try that. So we're focusing now on that 45%, and you can learn a lot from that 45% that impacts other cancers.

Transcript has been edited for clarity and conciseness.

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The overall survival rate in patients with melanoma has increased exponentially in the past decade. But thanks to the use of combinations in the treatment of melanoma, the future looks even brighter, according to one expert from the Melanoma Institute Australia.

Georgina Long of the University of Sydney recently spoke with 

’s sister publication, about what new combinations are currently being investigated and how the promise they hold could improve the treatment landscape for melanoma even further.

We’ve done well. We’ve now come from a five-year overall survival rate of less than 5% 10 years ago to now over 50% with combination, although it has toxicities. Our next step is to raise that bar further. We do want to aim towards 100% and zero deaths from melanoma.

So, looking at novel combinations, the platform that we think is exciting in the melanoma field, and that we are learning about at the Society of Melanoma Research, is the neoadjuvant platform, where we can assess doublets and triplets of novel therapies (and) within six weeks, get a pathological response readout, which we have already correlated with relapse-free survival for immunotherapies, and with that benchmarked, we can have a no-go or go decision as to whether further to explore combinations and triplets — and there are some exciting combinations coming up.

We know that TIL (tumor-infiltrating lymphocyte) therapy after PD-1 progression seems to have activity. We know there are other targets that we are looking at, targeted therapies besides BRAF, but VGF targets may complement our checkpoint inhibitors. And there are many intralesional treatments that work on the innate immune system, like toll-like receptor 9, that are under investigation.

So, there’s a lot of activity by specific antibodies, but there’s a lot of activity in this space, and we hope to achieve zero deaths from melanoma.

Dr. Georgina Long

Understanding How to Advance Immunotherapy Strategy Models in Melanoma

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